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9.B.180 The Tetra Spanning Protein 1 (Tts1) Family

The fission yeast Schizosaccharomyces pombe undergoes 'closed' mitosis where the nuclear envelope (NE) stays intact throughout chromosome segregation. Tts1, the fission yeast TMEM33 protein, has been implicated in organizing the peripheral endoplasmic reticulum (ER), but it also functions in remodeling the NE during mitosis (Zhang and Oliferenko 2014). Tts1 promotes insertion of spindle pole bodies (SPBs) in the NE at the onset of mitosis and modulates distribution of the nuclear pore complexes (NPCs; TC# 1.I.1)) during mitotic NE expansion. Structural features that drive partitioning of Tts1 to high-curvature ER domains are crucial for both aspects of its function. An amphipathic helix located at the C-terminus of Tts1 is important for ER shaping and modulating the mitotic NPC distribution. The evolutionarily conserved residues at the luminal interface of the third transmembrane region function specifically in promoting SPB-NE insertion (Zhang and Oliferenko 2014).

Endoplasmic reticulum (ER) stress leads to activation of the unfolded protein response signaling cascade and induction of apoptotic cell death and autophagy. Sakabe et al. 2015 showed that TMEM33, is in the ER, is ER stress-inducible and binds PERK. Overexpression correlates with increased expression of apoptotic signals including cleaved caspase-7, PARP and an autophagosome protein LC3II, and reduced expression of the autophagy marker p62. TMEM33 may function as a determinant of the ER stress-responsive events in cancer cells.

References associated with 9.B.180 family:

Sakabe, I., R. Hu, L. Jin, R. Clarke, and U.N. Kasid. (2015). TMEM33: a new stress-inducible endoplasmic reticulum transmembrane protein and modulator of the unfolded protein response signaling. Breast Cancer Res Treat 153: 285-297. 26268696
Urade, T., Y. Yamamoto, X. Zhang, Y. Ku, and T. Sakisaka. (2014). Identification and characterization of TMEM33 as a reticulon-binding protein. Kobe J Med Sci 60: E57-65. 25612671
Yamamoto, Y., A. Yoshida, N. Miyazaki, K. Iwasaki, and T. Sakisaka. (2014). Arl6IP1 has the ability to shape the mammalian ER membrane in a reticulon-like fashion. Biochem. J. 458: 69-79. 24262037
Zhang, D. and S. Oliferenko. (2014). Tts1, the fission yeast homologue of the TMEM33 family, functions in NE remodeling during mitosis. Mol. Biol. Cell 25: 2970-2983. 25103238